Primary lung cancer with radioiodine avidity: A thyroid cancer cohort study

BACKGROUND A proportion of lung cancers show sodium/iodide symporter(NIS)expression.Lung cancers with NIS expression may uptake radioiodine(RAI)and show RAIavid lesions on RAI scan for differentiated thyroid cancer(DTC)surveillance.AIM To investigate the possibility of RAI uptake by lung cancer in a cohort with thyroid cancer.METHODS RAI-avid lung cancers were analyzed using a prospectively maintained database of patients with thyroid cancer who were registered at a medical center between December 1,1976 and May 28,2018.NIS expression in lung cancer was assessed using immunohistochemical staining.RESULTS Of the 5000 patients with thyroid cancer from the studied dataset,4602 had DTC.During follow-up,33 patients developed primary lung cancer.Of these patients,nine received an iodine-131(131I)scan within 1 year before the diagnosis of lung cancer.One of these nine lung cancers was RAI-avid.NIS expression was evaluated,and three of the eight available lung cancers revealed NIS expression.The proportions of lung cancer cells with NIS expression were 60%,15%,and 10%.The RAI-avid lung cancer had the highest level of expression(60%).The RAI-avid lung cancer had a spiculated border upon single-photon emission computed tomography/computed tomography,which led to an accurate diagnosis.CONCLUSION A proportion of lung cancer demonstrates NIS expression and is RAI-avid.Clinicians should be aware of this possibility in the interpretation of RAI scintigraphy.

Grave’s Eye Ophthalmopathy Developing Following Radioiodine Therapy for Toxic Adenoma

The development of Grave’s ophthalmopathy following radioiodine treatment for Grave’s disease is well recognized. However, development of Grave’s ophthalmopathy following radioiodine therapy given for toxic adenoma or toxic nodular goiter has been reported but very rarely. Hereby, we reported a case of a 69-year-old male patient who developed ophthalmopathy after receiving 30 mCi (1110 mBq) 131 I radioiodine treatment for a toxic nodule. In addition, a review of the current literature with regards to this topic is presented.

Contribution of Radioiodine Thyroid Uptake and Scintigraphy to the Diagnosis of Hyperthyroidism

In total 184 studies, which included thyroid uptake and scintigraphy, were performed in 68 hyperthyroid patients: 67% female and 33% male to investigate their thyroid conditions. The aim of the present study was to illustrate the role of uptake and scintigraphy tests in determining the thyroid status of hyperthyroid patients. The uptake study was performed by oral administration of 100 - 200 μCi of 131I as sodium-iodide and counting the radioactivity at 2 and 24 hrs, whereas thyroid scintigraphy was performed 20 minutes after an intravenous injection of 2 - 4 mCi of 99mTc-pertechnetate. The present results of thyroid uptake and scintigraphy successfully identified the thyroid condition in different states. The present results were also compared with some reported data and found to be fair in good agreement.

Performance tests of a portable thyroid radioiodine

Objective:To evaluate the effectiveness of a portable thyroid radioiodine meter in on-site monitoring to enhance the monitoring precision of radioiodine inhaled by nuclear medicine staff and patients.Methods:A portable thyroid radioiodine meter was developed to measure the 131I activity in the thyroid.Performance tests of the portable thyroid radioiodine meter were conducted using calibration sources and testing methodologies adhering to national metrological standards.Results:The thyroid radioiodine meter exhibited integral non-linearity,8-h measurement stability,measurement linearity,and an energy resolution of 0.42%,1.05%,1.56%,and 7.11%,respectively for ^(137)Cs at 661.66 keV.Additionally,its minimum detectable activity for ^(131)I at 364.49 keV was approximately 22 Bq(10 min).Conclusion:The developed thyroid radioiodine meter features elevated performance and great potential for application in nuclear medicine and monitoring of responses to nuclear or radiological emergencies.

PANCYTOPENIA AFTER REPEATED RADIOIODINE TREATMENT ON METASTATIC THYROID CANCER TO BONE

The protocol and evaluation of I therapy have already been established, and it is quite effective in general for patients with metastatic thyroid cancer under 40 years old with fine or occult type of pulmonary metastases (papillary adenocarcinoma). However, the response of bone metastasis to I therapy is limited to only a part of tumors and is temporary in most cases although high I accumulation is visualized on scintigram. We have encountered a 65-year-old man with thyroid cancer. At the age of 61, follicular thyroid cancer with multiple bone metastasis was diagnosed, total thyroidectomy was carried out, and subsequently I therapy was performed. Bone pain diminished

Evaluation of therapeutic effectiveness of 131I-antiEGFR-BSA-PCL in a mouse model of colorectal cancer

AIM: To investigate the biological effects of internal irradiation, and the therapeutic effectiveness was assessed of ^(131)I-labeled anti-epidermal growth factor receptor(EGFR) liposomes, derived from cetuximab, when used as a tumor-targeting carrier in a colorectal cancer mouse model.METHODS: We described the liposomes and characterized their EGFR-targeted binding and cellular uptake in EGFR-overexpressing LS180 colorectal cancer cells. After intra-tumor injections of 74 MBq(740 MBq/m L) ^(131)I-anti EGFR-BSA-PCL, we investigated the biological effects of internal irradiation and the therapeutic efficacy of ^(131)I-anti EGFR-BSA-PCL on colorectal cancer in a male BALB/c mouse model. Tumor size, body weight, histopathology, and SPECT imaging were monitored for 33 d post-therapy.RESULTS: The rapid radioiodine uptake of ^(131)I-antiEGFR-BSA-PCL and ^(131)I-BSA-PCL reached maximum levels at 4 h after incubation, and the ^(131)I uptake of ^(131)I-anti EGFR-BSA-PCL was higher than that of ^(131)I-BSAPCL in vitro. The ^(131)I tissue distribution assay revealed that ^(131)I-anti EGFR-BSA-PCL was markedly taken up by the tumor. Furthermore, a tissue distribution assay revealed that ^(131)I-anti EGFR-BSA-PCL was markedly taken up by the tumor and reached its maximal uptake value of 21.0 ± 1.01 %ID/g(%ID/g is the percentage injected dose per gram of tissue) at 72 h following therapy; the drug concentration in the tumor was higher than that in the liver, heart, colon, or spleen. Tumor size measurements showed that tumor development was significantly inhibited by treatments with ^(131)I-anti EGFR-BSA-PCL and ^(131)I-BSA-PCL. The volume of tumor increased, and treatment rate with ^(131)I-anti EGFR-BSA-PCL was 124% ± 7%, lower than that with ^(131)I-BSA-PCL(127% ± 9%), ^(131)I(143% ± 7%), and normal saline(146% ± 10%). The percentage losses in original body weights were 39% ± 3%, 41% ± 4%, 49% ± 5%, and 55% ± 13%, respectively. The best survival and cure rates were obtained in the group treated with ^(131)I-anti EGFR-BSA-PCL. The animals injected with ^(131)I-anti EGFR-BSA-PCL and ^(131)I-BSA-PCL showed more uniform focused liposome distribution within the tumor area.CONCLUSION: This study demonstrated the potential beneficial application of ^(131)I-anti EGFR-BSA-PCL for treating colorectal cancer. ^(131)I-anti EGFR-BSA-PCL suppressed the development of xenografted colorectal cancer in nude mice, thereby providing a novel candidate for receptor-mediated targeted radiotherapy.

Formation of AgI/Ag_3PO_4 solid solution on alumina for enhancing radioactive iodine adsorption at high temperatures

Radioiodine-131 is one of the pernicious radionuclides released during nuclear accidents, as its radioactivity can potentially affect public health and safety.To prevent radioiodine-131 from being released into the environment, the use of adsorbents that are highly efficient at high temperatures is significantly important. The radioactive gas from the nuclear core in an accident, such as the Fukushima nuclear accident, is usually released occurs under high-temperature conditions. Therefore, in this study, a 10 wt% silver phosphate-loaded alumina(Ag_3 PO_4/Al_2 O_3) adsorbent was prepared. Further, its performance toward radioiodine adsorption was tested at high temperatures up to 750 0 C, using Al_2 O_3 and traditional 10 wt% Ag/Al_2 O_3 adsorbent as controls. The results of the iodine adsorption test indicated that the 10 wt% Ag_3 PO_4/Al_2 O_3 adsorbent showed a higher decontamination factor than did the 10 wt% Ag/Al_2 O_3 adsorbent by two orders of magnitude at 650 and 750℃. Results of the iodine desorption test revealed that the new adsorbent could be effectively used at 750 ℃. The characteristic powder X-ray diffraction, nitrogen adsorption-desorption isotherm,X-ray photoelectron spectroscopy, and thermogravimetric analysis-differential scanning calorimetry data indicated that the enhanced adsorption ability at high temperatures was attributed to the formation of a solid solution between silver iodide and Ag_3 PO_4.

Does the use of recombinant TSH in preparation for I-131 scintigraphy scan affect hearing function?

Objective: The objective of this study was to examine the effect of hypothyroidism on hearing function in patients surgically treated for differentiated thyroid cancer and subsequently experienced hypothyroidism during preparation for follow up I-131 scintigraphy scan by either recombinant human thyroid stimulating hormone(rhTSH) treatment or thyroid hormone withdrawal(THW).Methods: A total of 55 patients undergoing I-131 scintigraphy scan following surgeries for differentiated thyroid cancer were included in the study, including 25 patients prepared by administration of recombinant TSH(rhTSH Group) and 30 patients by thyroid hormone withdrawal(THW Group).Results: Air conduction thresholds at 1, 2 and 4 kHz for both ears were higher during hypothyroid period than during euthyroid period for patients in the THW group(p < 0.05) but not for patients in the rhTSH group.Conclusion: Sensorineural hearing loss was detected, especially at low frequencies, in patients with DTC after surgical treatment whose hormone replacement therapy was withdrawn but not in those receiving rhTSH. It is therefore preferred to use rhTSH when preparing for I-131 scintigraphy scan in patients at risk for hearing loss.

^(125)I(^(131)I)标记血卟啉的研制

为了研究光敏剂血卟啉在组织内的分布状况及运动变化规律等,以提高疗效,按文献制备了放射性标记的血卟啉作为“示踪剂”。1 碘化标记1)氯胺T法:反应所用的氯胺T（ChT）,Na2S2O5,KI等均用0.2mol/L pH7.5PB溶解,临用前配制.小试管中放入血卟啉0.5mL（5mg/mL,针剂,中国医学科学院肿瘤研究所提供）、Na125I(Na131I)25μL（约2mCi）和ChT0.5mL（5mg/mL）。

Internal radiation therapy:a neglected aspect of nuclear medicine in the molecular era

With increasing evidence, internal radiation therapy, also known as brachytherapy, has become a neglected aspect of nuclear medicine in the molecular era. In this paper, recent developments regarding internal radiation ther- apy, including developments in radioiodine-13l （131^I） and thyroid, radioimmunotherapy （RIT） for non-Hodgkin lym- phoma （NHL）, and radiopharmaceuticals for bone metastases. Relevant differences and status of their applications in China were mentioned as well. These molecular mediated internal radiation therapies are gaining increasing importance by providing palliative and curative treatments for an increasing number of diseases and becoming one of the important parts of molecular nuclear medicine.

A Novel Technique for the Preparation of ^(125)I-5-trimethylstannyl-1-(2-deoxy-2-fluoro-beta-D-arabino-furanosyl) Urail and Its Biodistribution Pattern in Kunming Mice

In this study, a novel technique for the preparation of 125I-5-trimethylstannyl-1-（2-deoxy-2-fluoro-beta-D-arabinofuranosyl） urail （FIAU） was developed, 125I-FIAU biodistribution profile was detected in Kunming mice and the possibility of using FTAU radio-labeling for reporter gene imaging was explored. 5-trimethylstannyl-1-（2-deoxy-2-fluoro-beta-D-arabinofuranosyl） urail （FTAU） was labeled with radioiodine （125I）. A rotary evaporation method was used to remove excess methanol. The reactant was purified through a Sep-Pak C18 reversal phase column. The radiochemical purity and in vivo stability were determined using silica gel thin layer chromatography （TLC）. The biodistribution of 125I-FIAU in Kunming mice was also detected. The results showed that 125I-FIAU could be radiolabeled effectively with FTAU, with mean labeling rate being （81±0.38）% （n =5）. The mean radiochemical purity of （98.01±0.40）% （n=5） was achieved after a reversal phase Sep-park column purification. 125I-FIAU was stable when incubated in normal human serum or in saline at 37°C, with a radiochemical purity 〉96% during a 0.5-24 h time period. Biological experiments exhibited rapid clearance of 125I-FIAU from the blood pool. 125I-FIAU was mostly excreted by kidneys. 125I-FIAU in myocardium dropped conspicuously after 8 h and there was hardly retention at 24 h. We were led to concluded that the new method of radioiodinization of FTAU for the preparation of 125I-FIAU is easy, highly effective and stable in vivo. The biodistribution of 125I-FIAU in Kunming mice showed it can serve as an imaging probe for myocardial reporter genes.

The Relationship of Age and Clinicopathologic Pattern to the Aggressiveness of Thyroid Cancer

Objective: To study the relation of age and clinicopathologic pattern to the aggressiveness of thyroid cancer cases and the treatment results of patients from western region of Saudi Arabia with differentiated thyroid carcinoma referred for treatment in King Abdulaziz Hospital and Oncology Center, Jeddah, Saudi Arabia. Methods: Retrospective review of 174 patients with differentiated thyroid carcinoma and analysis of the clinicopathologic characteristics, age correlation to different risk factors, treatment protocol and results were performed. Results: Analysis of the clinicopathologic pattern showed no statistically significant difference between patients in the different age groups except for extrathyroid extension and lymph node involvement. Patients older than 45 years had a statistically significant lower incidence of nodal involvement and a higher rate of extrathyroid extension (<0.02). In this study, we used a high dose method (Radioiodine-131 dose 75 - 100 mCi) for thyroid remnant ablation after thyroidectomy (total or near total) in 134 patients. An Iodine-131 dose of 200 mCi was used in 8 patients with distant metastases. In 24 patients with radioiodine-avid cervical lymph nodes and six patients with a gross residual tumor, an Iodine-131 dose of 150 mCi was used. For the whole study group, the 5-year overall survival and disease-free survival were 96% and 88%. Conclusion: Despite the fact that differentiated thyroid carcinoma is among the most curable cancer some patients are still at high risk for recurrent and increased mortality.

Effects of BRAF^(V600E) Mutation on Na^+/I^- Symporter Expression in Papillary Thyroid Carcinoma

Radioiodine ablation（RIA） therapy is one of the most important treatments for papillary thyroid carcinoma（PTC）, but some patients who received 131 I have radioiodine-refractory disease caused by the decreased expression of the Na^＋/I^- symporter（NIS）. BRAF^V600E mutation is one possible risk factor that can disturb the NIS expression, but the roles are unclear in clinical practice. This research discussed the association of BRAF^V600E mutation and NIS expression in PTC tissue and the clinical implications in RIA therapy. 134 PTC samples were collected between June 2013 and June 2014 from Tongji Hospital affiliated to Tongji Medical College, and their clinical characteristics were analyzed. RT-PCR was used to detect the BRAF^V600E mutation from formalin-fixed paraffin-embedded samples, and immunohistochemistry was applied to detect the NIS expression. IPP software was used to calculate the relative expression quantity of NIS. We found that there was no significant correlation between the absorbance（A） values of NIS and clinicopathologic features in these cases, even thyroid stimulating hormone. BRAF^V600E mutation showed inhibitory effect on the NIS expression without statistically significant difference in all PTC cases（β=–0.0195, P=0.085）, but in the subgroup without hashimoto＇s thyroiditis（HT）, BRAF^V600E mutation could significantly inhibit the NIS expression（β=–0.0257, P=0.046）. The results indicate that BRAF^V600E mutation is correlated with a lower expression of NIS in PTCs without HT, suggesting the radioiodine-refractory effects during RIA therapy in these patients.

Radioiodination and biological evaluation of valsartan as a tracer for cardiovascular disorder detection

A procedure for radioiodination of valsartan with iodine-125 is carried out via an electrophilic substitution of hydrogen atom with the iodonium cation I+. All reaction parameters were studied to optimize the labeling conditions of valsartan and to obtain a maximum radiochemical yield (RCY) of the 125I-Valsartan [125I-Val]. By using 3.7 MBq of Na125I, 50 μg of valsartan (0.2 mM) as substrate, 25 μg of Iodogen (0.15 mM) as oxidizing agent in ethanol at room temperature for 30 min, the radiochemical yield of 125I-Val was 98.6% The radiochemical yield was determined by electrophoresis using cellulose acetate moistened with 0.02 M phosphate buffer pH 7. The labeled compound was separated and purified by means of high-pressure liquid chromatography (HPLC). The biological distribution in normal mice indicates the suitability of radioiodinated valsartan to image any cardiovascular disorders.

Radioiodination of Cephalexin with ¹²⁵I and Its Biological Behavior in Mice

A procedure for radioiodination of Cephalexin with iodine-125 was carried out via an electrophilic substitution reaction. Using 3.7 MBq of Na125I, 200μl of cephalexin as substrate, 200 μl of iodogen as oxidizing agent in acetone at 40°C for 20 min, a maximum radiochemical yield of 125I-Ceph (95%) was obtained. The labeled compound was separated and purified by means of high-pressure liquid chromatography (HPLC). The biological distribution in normal and inflamed (septic and aseptic) mice indicates the suitability of radioiodinated cephalexin for imaging of

Postoperative Stimulated Thyroglobulin Level and Recurrence Risk Stratification in Differentiated Thyroid Cancer

Background： Postoperative preablative stimulated thyroglobulin （ps-Tg） has been evaluated in predicting prognosis and success of ablation regarding differentiated thyroid cancer （DTC）; however, its relationship with recurrence risk and radioiodine decision-making remains uncertain, especially in Chinese DTC patients. We aimed to evaluate the association between ps-Tg and recurrence risk stratification in DTC, to provide incremental values for ps-Tg in postoperative assessment and radioiodine management. Methods： Seven hundred and seven patients with DTC were included; low-risk （L; n = 90）, intermediate-risk （I; n = 283）, and high-risk （H; n = 334, 117 with distant metastasis [M 1 ]） patients were divided according to recurrence risk stratification. The M 1 group was further analyzed regarding evidence of metastasis. Cut-off values of ps-Tg were obtained using receiver operating characteristic analysis. Results： Patients with more advanced disease at initial risk stratification were more likely to have higher ps-Tg levels （I vs. L： P 〈 0.05; H vs. 1： P 〈 0.001; H vs. L： P 〈 0.001）. The corresponding cut-off value of ps-Tg for distinguishing sensitivity and specificity in each of the two groups was 2.95 ng/ml （1 vs. L： 61.5%, 63.3%）, 29.5 ng/ml （H vs, I： 41.9%, 92.6%）, 47.1 ng/ml （M1 vs. M0 in the H group： 79.5%, 88.9%） and 47.1 ng/ml （MI vs. M0 in all patients： 79.5%, 93.7%）. With the cut-offvalue at 47.1 ng/ml, ps-Tg was the only factor that could be used to identify distant metastases, and consequently if measured before radioiodine therapy would prevent 10.26% of patients with M1 from undertreatment, Conclusions： Ps-Tg, as an ongoing reassessment marker, favors differential recurrence risk grading and provides incremental values for radioiodine treatment decision-making.

Radioiodinated tyrosine based carbon dots with efficient renal clearance for single photon emission computed tomography of tumor

Nan oparticles with effective tumor accumulation and efficient renal clearance have attracted significant interests for clinical applications.Weprepared 2.5 nm tyrosine based carbon dots(TCDs)with phenolic hydroxyl groups on the surface for directly 125I labeling.The 125I labeledpolyethylene glycol(PEG)functionalized TCDs(125I-TCDPEGs)showed excellent radiochemical stability both in vitro and in vivo.Due to theenhanced permeability and retentio n effect,these 125I-TCDPEGs demonstrated a tumor accumulatio n around 4%-5%of the injected doseper gram(ID/g)for U87MG,4T1,HepG2 and MCF7 tumor-bearing mice at 1 h post-injection.Meanwhile,the 125I-TCDPEGs also could befast renally excreted,with less than 0.6%ID/g left in the liver and spleen within 24 h.These radioactive carb on dots not only can be used forcellular fluorescence imaging due to their intrinsic optical property,but are also effective single photon emission computed tomography(SPECT)imaging agents for tumor.Together with their excellent biocompatibility and stability,we anticipate these 125I-TCDPEGs of great potential for earlytumor diagnosis in clinic.Whafs more,our TCDPEGs are also proved to be feasible carriers for other iodine isotopes such as 127I and 131I fordifferent biomedical application.

Evaluation of necrosis avidity of radioiodinated 5-hydroxytryptophan and its potential applications in myocardial infarction imaging

This study aimed to seek necrosis avid agents with high safety from DNA binding agents. The interaction of 5-hydroxytryptophan(5-HTP) with DNA was investigated by a series of spectroscopic studies. Then, 5-HTP was labeled with iodine-131([^(131)I]5-HTP) and the necrosis avidity of [^(131)I]5-HTP was evaluated by in vitro cell binding assays, in vivo biodistribution experiments and blocking experiment. Finally, the potential of [^(131)I]5-HTP to image necrotic myocardium was explored in rat models with myocardial infarction by SPECT/CT imaging. Results showed that 5-HTP bound to DNA in groove binding mode and the binding constant was 1.69×10~4 L/mol. [~(^(131))I]5-HTP showed specific affinity to necrotic A549 cells,which might be related to cell nucleus. Biodistribution and autoradiography results showed preferential accumulation of [^(131)I]5-HTP in necrotic muscle(necrotic/viable muscle ratio: 6.95 ? 0.68 at 3 h postinjection(p.i.)), which could be blocked by 5-HTP with 66.7% decline, indicating that [^(131)I]5-HTP might share the same necrotic targets with 5-HTP. On SPECT/CT images, a hotspot was clearly observed at 3h p.i.in the necrotic myocardium while not in the control myocardium. In conclusion, [^(131) I]5-HTP is a novel necrosis avid agent and can rapidly visualize necrotic myocardium at 3 h p.i. The necrosis avidity mechanism of [^(131) I]5-HTP may be attributed to its interactions with exposed DNA in the necrotic tissues.